CA2589085C - Cathepsin cysteine protease inhibitors - Google Patents

Cathepsin cysteine protease inhibitors Download PDF

Info

Publication number
CA2589085C
CA2589085C CA2589085A CA2589085A CA2589085C CA 2589085 C CA2589085 C CA 2589085C CA 2589085 A CA2589085 A CA 2589085A CA 2589085 A CA2589085 A CA 2589085A CA 2589085 C CA2589085 C CA 2589085C
Authority
CA
Canada
Prior art keywords
fluoro
trifluoro
leucinamide
biphenyl
cyanocyclopropyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
CA2589085A
Other languages
English (en)
French (fr)
Other versions
CA2589085A1 (en
Inventor
Jacques-Yves Gauthier
Chun Sing Li
Christophe Mellon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Canada Inc
Original Assignee
Merck Canada Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Canada Inc filed Critical Merck Canada Inc
Publication of CA2589085A1 publication Critical patent/CA2589085A1/en
Application granted granted Critical
Publication of CA2589085C publication Critical patent/CA2589085C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/275—Nitriles; Isonitriles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Pulmonology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)
CA2589085A 2004-11-23 2005-11-18 Cathepsin cysteine protease inhibitors Expired - Lifetime CA2589085C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US63040504P 2004-11-23 2004-11-23
US60/630,405 2004-11-23
PCT/CA2005/001764 WO2006056047A1 (en) 2004-11-23 2005-11-18 Cathepsin cysteine protease inhibitors

Publications (2)

Publication Number Publication Date
CA2589085A1 CA2589085A1 (en) 2006-06-01
CA2589085C true CA2589085C (en) 2014-04-29

Family

ID=36497694

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2589085A Expired - Lifetime CA2589085C (en) 2004-11-23 2005-11-18 Cathepsin cysteine protease inhibitors

Country Status (24)

Country Link
US (2) US20070293578A1 (da)
EP (1) EP1817276B1 (da)
JP (1) JP5055488B2 (da)
KR (1) KR20070085435A (da)
CN (2) CN101061093A (da)
AR (1) AR055283A1 (da)
AU (1) AU2005309267B2 (da)
BR (1) BRPI0518054A (da)
CA (1) CA2589085C (da)
DK (1) DK1817276T3 (da)
ES (1) ES2394618T3 (da)
IL (1) IL183308A (da)
MX (1) MX2007006136A (da)
MY (1) MY137717A (da)
NO (1) NO339125B1 (da)
NZ (1) NZ554872A (da)
PE (1) PE20061054A1 (da)
PL (1) PL1817276T3 (da)
PT (1) PT1817276E (da)
RU (1) RU2399613C2 (da)
SI (1) SI1817276T1 (da)
TW (1) TWI353244B (da)
WO (1) WO2006056047A1 (da)
ZA (1) ZA200703530B (da)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4201716B2 (ja) * 2002-03-05 2008-12-24 メルク フロスト カナダ リミテツド カテプシンシステインプロテアーゼ阻害剤
BRPI0410979A (pt) * 2003-09-18 2006-07-04 Axys Pharm Inc composto, composição farmacêutica, e, métodos para tratar uma doença em um animal mediada pela catepsina s e para tratar um paciente submetido a uma terapia
EP1817275A1 (en) * 2004-12-01 2007-08-15 Schering Aktiengesellschaft Haloalkyl containing compounds as cysteine protease inhibitors
WO2006060810A1 (en) * 2004-12-02 2006-06-08 Schering Aktiengesellschaft Sulfonamide compounds as cysteine protease inhibitors
US20090005323A1 (en) * 2005-01-19 2009-01-01 Michael David Percival Cathepsin K Inhibitors and Obesity
US8722734B2 (en) * 2005-03-02 2014-05-13 Merck Sharp & Dohme Corp. Composition for inhibition of cathepsin K
WO2006102243A2 (en) * 2005-03-21 2006-09-28 Applera Corporation Alpha ketoamide compounds as cysteine protease inhibitors
EP1866277B1 (en) * 2005-03-22 2014-06-25 Virobay, Inc. Sulfonyl containing compounds as cysteine protease inhibitors
EP2077869B1 (en) * 2006-08-28 2015-02-25 Akademia Medyczna Im. Piastow Slaskich We Wroclaw iu A system for the extra-corporeal purification of blood of pathogenic enzymes
WO2008037072A1 (en) 2006-09-25 2008-04-03 Merck Frosst Canada Ltd. Cathepsin b inhibitors
US7893112B2 (en) * 2006-10-04 2011-02-22 Virobay, Inc. Di-fluoro containing compounds as cysteine protease inhibitors
ZA200902477B (en) * 2006-10-04 2010-08-25 Virobay Inc Di-fluoro containing compounds as cysteine protease inhibitors
WO2009065098A1 (en) * 2007-11-16 2009-05-22 Velcura Therapeutics, Inc. Use of cathepsin k antagonists in the treatment of bone cancer
WO2010056877A2 (en) * 2008-11-13 2010-05-20 Virobay, Inc. Haloalkyl containing compounds as cysteine protease inhibitors
US8324417B2 (en) * 2009-08-19 2012-12-04 Virobay, Inc. Process for the preparation of (S)-2-amino-5-cyclopropyl-4,4-difluoropentanoic acid and alkyl esters and acid salts thereof
WO2012158784A2 (en) 2011-05-16 2012-11-22 Theodore Mark Kamenecka Modulators of the nuclear hormone receptor ror
CN106916091B (zh) * 2015-12-24 2020-10-09 广东东阳光药业有限公司 组织蛋白酶k抑制剂及其用途
US11766467B2 (en) 2017-09-01 2023-09-26 University Of Wyoming Methods of treating wounds using cathepsin K inhibitors
US10758559B1 (en) * 2017-09-01 2020-09-01 University Of Wyoming Targeting cathepsin K to facilitate wound healing
CA3107947A1 (en) 2018-08-02 2020-02-06 Intervet International B.V. Process to make a selective cathepsin cysteine protease inhibitor
CA3107899A1 (en) 2018-08-02 2020-02-06 Intervet International B.V. Crystalline forms of n1-(1-cyanocycloproply)-n2-((1s)-1-{4'-[(1r-2,2-difluoro-1-hydroxyethyl]biphenyl-4-yl}-2,2,2-trifluoroethyl)-4-fluoro-l-leucinamide
AU2020250933A1 (en) 2019-04-05 2021-10-28 Centre Hospitalier Régional Et Universitaire De Brest Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning
CN112438972B (zh) * 2019-08-29 2021-07-30 沈阳药科大学 组织蛋白酶抑制剂的医药用途
CN113462728B (zh) * 2021-07-09 2024-06-07 浙江工业大学 一种利用土星轮头酵母制备(r)-1-(4-溴苯基)-2,2,2-三氟乙醇的方法
CN116462570B (zh) * 2023-03-14 2025-06-24 昆明理工大学 一种α-二氟甲基苯乙烯衍生物及其制备方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUP0004400A3 (en) * 1997-11-05 2002-10-28 Novartis Ag Dipeptide nitriles, process for their preparation, pharmaceutical compositions comprising thereof and their use
JP4365094B2 (ja) * 2001-03-02 2009-11-18 メルク フロスト カナダ リミテツド カテプシンシステインプロテアーゼ阻害薬
US7302587B2 (en) * 2001-06-08 2007-11-27 Matra Transport International Secure computer system
DE60225316T2 (de) * 2001-11-13 2009-02-26 AXYS Pharmaceuticals, Inc., South San Francisco Cyanoalkylamino-derivate als protease-hemmer
JP4201716B2 (ja) 2002-03-05 2008-12-24 メルク フロスト カナダ リミテツド カテプシンシステインプロテアーゼ阻害剤
CA2506114A1 (en) * 2002-12-05 2004-06-24 Axys Pharmaceuticals, Inc. Cyanomethyl derivatives as cysteine protease inhibitors
BRPI0410979A (pt) * 2003-09-18 2006-07-04 Axys Pharm Inc composto, composição farmacêutica, e, métodos para tratar uma doença em um animal mediada pela catepsina s e para tratar um paciente submetido a uma terapia
US8722734B2 (en) * 2005-03-02 2014-05-13 Merck Sharp & Dohme Corp. Composition for inhibition of cathepsin K

Also Published As

Publication number Publication date
NZ554872A (en) 2010-12-24
AR055283A1 (es) 2007-08-15
RU2007123611A (ru) 2008-12-27
RU2399613C2 (ru) 2010-09-20
US7407959B2 (en) 2008-08-05
AU2005309267B2 (en) 2011-05-12
WO2006056047A1 (en) 2006-06-01
MX2007006136A (es) 2007-07-19
IL183308A0 (en) 2007-09-20
ES2394618T3 (es) 2013-02-04
CN102391151A (zh) 2012-03-28
PL1817276T3 (pl) 2012-12-31
TWI353244B (en) 2011-12-01
AU2005309267A1 (en) 2006-06-01
EP1817276A4 (en) 2009-12-09
EP1817276A1 (en) 2007-08-15
US20060111440A1 (en) 2006-05-25
IL183308A (en) 2013-05-30
ZA200703530B (en) 2008-01-08
WO2006056047A9 (en) 2007-06-21
PE20061054A1 (es) 2006-10-20
US20070293578A1 (en) 2007-12-20
EP1817276B1 (en) 2012-08-08
NO20073222L (no) 2007-08-03
TW200631576A (en) 2006-09-16
PT1817276E (pt) 2012-10-25
SI1817276T1 (sl) 2012-12-31
CA2589085A1 (en) 2006-06-01
JP2008520590A (ja) 2008-06-19
NO339125B1 (no) 2016-11-14
BRPI0518054A (pt) 2008-10-28
DK1817276T3 (da) 2012-11-19
CN101061093A (zh) 2007-10-24
JP5055488B2 (ja) 2012-10-24
MY137717A (en) 2009-03-31
KR20070085435A (ko) 2007-08-27

Similar Documents

Publication Publication Date Title
EP1817276B1 (en) Cathepsin cysteine protease inhibitors
EP2675440B1 (en) Cathepsin cysteine protease inhibitors
EP1694647B1 (en) Cathepsin cysteine protease inhibitors
CA2535366A1 (en) Cathepsin inhibitors
EP1644326B1 (en) Cathepsin cysteine protease inhibitors
CA2535359A1 (en) Cathepsin cysteine protease inhibitors
EP1902031B1 (en) Cathepsin cysteine protease inhibitors
US20100063013A1 (en) Cathepsin cysteine protease inhibitors
US20090253672A1 (en) Cathepsin Cysteine Protease Inhibitors

Legal Events

Date Code Title Description
EEER Examination request
H11 Ip right ceased following rejected request for revival

Free format text: ST27 STATUS EVENT CODE: T-6-6-H10-H11-H101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: TIME LIMIT FOR REVERSAL EXPIRED

Effective date: 20250521

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: N-6-6-W10-W00-W100 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: LETTER SENT

Effective date: 20251024